Epinephrine synthesis by an N-methyltransferase in rat liver

We investigated if liver can synthesize epinephrine in vitro and in vivo. Homogenates of rat liver readily synthesized [3H]epinephrine from [3H]S-adenosylmethionine and norepinephrine. Liver homogenates also N-methylated dopamine at more than twice the rate that they N-methylated norepinephrine. In contrast, adrenal homogenates, which N-methylate norepinephrine to form epinephrine using the enzyme phenylethanolamine-N-methyltransferase (PNMT), methylated dopamine only about 1% as well as norepinephrine. Synthesis of epinephrine by liver homogenates was not significantly inhibited by the PNMT inhibitor SKF 29661 at a concentration that inhibited adrenal homogenate epinephrine synthesis by nearly 90%. These findings indicate that liver can synthesize epinephrine in vitro using an enzyme other than PNMT. Adrenal demedullation of rats reduced plasma epinephrine levels to 7% of control values, but left liver epinephrine and epinephrine-forming enzyme levels unchanged. Treatment of demedullated rats with 6-hydroxydopamine plus reserpine also resulted in dramatically reduced plasma epinephrine levels but no change in hepatic epinephrine and N-methylating enzyme levels. We conclude that the liver synthesizes its own epinephrine.